AB SCIENCE (AB) Status Update summary

Platform and Compound Overview

• Three platforms: neurodegenerative (masitinib), hematology/oncology (AB8939), and a drug discovery platform for neurodegenerative diseases.

• AB8939 is a novel compound with dual mechanisms: microtubule destabilization and ALDH inhibition, targeting both proliferating and stem cells in AML.

• AB8939 is not degraded by myeloperoxidase and avoids P-gp mediated drug resistance, making it suitable for AML.

• AB8939 demonstrates activity in both chemotherapy-naive and refractory AML cells, including those resistant to Ara-C.

Preclinical and Clinical Data

• AB8939 demonstrated efficacy in killing azacitidine-resistant AML cell lines and in vivo mouse models, with low toxicity to normal cells.

• Preclinical and early clinical data show AB8939 eradicates leukemia blasts and cancer stem cells, with additive effects when combined with azacitidine or venetoclax.

• Combination with Vidaza or venetoclax in mice showed additive or synergistic effects, with the triplet therapy planned for clinical testing.

• AB8939 effectively targets and eliminates leukemia stem cells, potentially preventing relapse.

• Phase 1 studies indicate AB8939 is well-tolerated, with low hematological toxicity and promising efficacy in both MECOM and non-MECOM AML patients.

Clinical Development and Case Studies

• Phase I completed dose escalation (3 and 14 days), showing safety and initial efficacy; next step is combination therapy.

• Case reports show partial and deep responses in refractory AML patients, including those with adverse cytogenetics, with preserved blood counts and prolonged survival.

• AB8939 demonstrates activity in both chemotherapy-naive and refractory AML cells, including those resistant to Ara-C.